Lipids and Myeloid Cell Function in Cancer

项目摘要 髓系细胞是肿瘤微环境的重要组成部分。在生理条件下，这些细胞 由成熟的终末分化细胞组成：中性粒细胞(PMN)和其他 粒细胞；巨噬细胞(MΦ)；树突状细胞(DC)。在癌症中，髓系隔室显著 它现在被认为是癌症的主要免疫学标志之一。荷瘤 (TB)宿主蓄积免疫抑制M-Φ，肿瘤中DC诱导强效免疫无效 回应。在癌症中，髓系室的显著变化是病理上的 激活的未成熟髓系细胞具有强大的抑制免疫反应的能力-髓系来源 抑制细胞(MDSC)。在结核病小鼠中，MDSC的总群体由三组细胞组成： 最丰富的(&gt；75%)未成熟的、病理激活的中性粒细胞(PMN-MDSC)；较少的(&lt；20%) 病理激活的单核细胞群体(M-MDSC)；早期髓系小群体(&lt；5%) 先驱物。目前的观点单独考虑髓系细胞的变化。不同的机制应用于 不同的细胞。我们知识上的差距是这些不同的髓系细胞如何相互作用 在荷瘤宿主中。在这项提案中，我们将检验氧化脂质可能提供桥梁的假设 在癌症中不同群体的髓系细胞之间的关系，并协调它们的异常功能。 这个项目的最终目标不仅是为了更好地了解调节髓系细胞的机制 在癌症中发挥作用，但开发新的方法来调节癌症的免疫反应。 为实现这一目标，我们提出了以下具体目标： 具体目的1.确定凝集素型氧化型低密度脂蛋白受体1在PMN-MDSC调节中的作用 癌症患者 明确氧化脂质在PMN-MDSC和DC功能中的作用。

Project Summary Myeloid cells are critical component of tumor microenvironment. Under physiological conditions these cells are comprised of mature terminally differentiated cells: polymorphonuclear neutrophils (PMN) and other granulocytes; macrophages (MΦ); and dendritic cells (DCs). In cancer, myeloid compartment is dramatically affected, which is now considered as one of the major immunological hallmarks of cancer. Tumor-bearing (TB) hosts accumulate immunosuppressive MΦ, DCs in cancer are ineffective in induction of potent immune responses. The prominent change in the myeloid compartment in cancer is the expansion of pathologically activated immature myeloid cells with the potent ability to suppress immune responses – myeloid-derived suppressor cells (MDSC). In TB mice, the total population of MDSC consists of three groups of cells: the most abundant (>75%) immature, pathologically activated neutrophils (PMN-MDSC); less abundant (<20%) population of pathologically activated monocytes - (M-MDSC); and small (<5%) population of early myeloid precursors. The current view considers changes in myeloid cells separately. Different mechanisms applied to the different cells. The gap in our knowledge is how these different myeloid cells can interact with each other in tumor-bearing hosts. In this proposal we will test the hypothesis that oxidized lipids may provide bridge between different populations of myeloid cells in cancer and orchestrate their abnormal function. The ultimate goal of this project is not only to better understand the mechanism regulating myeloid cell function in cancer but to develop novel approaches to regulation of immune responses in cancer. To achieve this goal we propose the following specific aims: Specific aim 1. To determine the role of lectin-type oxidized LDL receptor 1 in regulation of PMN-MDSC in cancer patients Specific aim 2. To identify the role of oxidized lipids in the function of PMN-MDSC and DCs.